tbuckley/cabot-search huggingface dataset:
AB0835 CAPILLAROSCOPIC FINDINGS IN PATIENTS WITH SJÖGREN’S SYNDROME, SYSTEMIC SCLEROSIS, AND PRIMARY RAYNAUD’S PHENOMENON IN A HIGH-COMPLEXITY CENTER IN MEDELLÍN, COLOMBIA 2016-2022
Authors: S. Hoyos-Patiño, A. Arango-Martínez, L. M. Rodríguez Padilla, A. Chavarriaga Restrepo, C. J. Velásquez-Franco
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In Sjögren's syndrome (SS), it has been suggested that capillaroscopy could be useful to identify patients with characteristics of overlap syndromes and risk of evolving into another connective tissue disease, in addition to determine extraglandular systemic involvement. The published information is scarce, as its comparison with systemic sclerosis (SSc) and primary Raynaud's phenomenon (pRP); in addition, different optical instruments other than the videocapillaroscope with 200x magnification have been used. <h3>Objectives</h3> To assess capillaroscopic findings in patients with SS compared to subjects with SSc and pRP at a national capillaroscopy reference center in Medellín, Colombia, between 2016 and 2022. <h3>Methods</h3> An analytical cross-sectional observational study was carried out. Patients over 18 years who met 2016 ACR/EULAR, 2013 ACR/EULAR, and 2014 international criteria for SS, SSc, and pRP, respectively, confirmed by a rheumatologist, were included. Capillaroscopic variables were analyzed (number of capillaries per millimeter, dilated capillaries, megacapillaries, abnormal capillaries, microhemorrhages, avascular zones, arborescent capillaries, capillary disorganization, and capillaroscopic pattern). Qualitative variables were expressed by absolute and relative frequencies and the quantitative by the median and interquartile range (IQR) due to the heterogeneous distribution of data. <h3>Results</h3> In total, there were 195 patients, of which 181 (92.8%) were female; the median age was 53 years (IQR:39-62). The most frequent capillaroscopic finding in SS was the presence of dilated capillaries (n=36; 55.4%). A higher frequency of global capillaroscopic abnormalities was observed in the SSc group compared to the other groups (p&lt;0.0001 in all comparisons). There was no difference in the frequency of arborescent capillaries between the SS and SSc groups. In the SS group, either scleroderma pattern was found in 18.5% (n=12) (Table). <h3>Conclusion</h3> Patients with SSc and SS have a high prevalence of capillaroscopic abnormalities with statistically significant differences compared to the pRP group. The high frequency of dilated capillaries in SS stands out, as well as common arborescent capillaries and scleroderma patterns. <h3>References</h3> [1]Melsens K et al. Clin Exp Rheumatol. 2020;38 Suppl 126(4):150-157. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1136 MORTALITY IN PATIENTS WITH PSORIATIC ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: H. Huang, W. Xie, Y. Geng, Y. Fan, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> It remains debated whether patients with psoriatic arthritis (PsA) are at greater risk of mortality. <h3>Objectives</h3> We aimed to determine the magnitude of all-cause mortality risk in patients with PsA compared with the general population through a systematic review and meta-analysis. <h3>Methods</h3> We searched Pubmed, EMBASE and Cochrane Library for studies published from inception to April 2022. STATA meta-analysis software was used to calculate the pooled risk estimates for mortality (standardized mortality ratio, SMR). To address the potential heterogeneity, χ2 test, I2 statistics, subgroup analysis and sensitivity analysis were used. <h3>Results</h3> Our search identified 3235 articles, of which 18 studies with 134355 patients were eventually included for the analysis. A total of 7518 deaths were observed. Overall, we found a 1.13-fold increased risk of death in PsA patients when compared with the general population (meta-SMR: 1.13, 95% CI 1.03-1.25). Subgroup analyses showed that summary meta-SMR was higher in female patients (1.24 [95% CI 1.10-1.39]; I²=49.7%) than male patients (0.92 [95% CI 0.62-1.37]; I²=73.8%). <h3>Conclusion</h3> The existing data indicated approximately 13% increase of mortality among patients with PsA compared with the general population. More attention should be paid to those patients with risky characteristics. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Replication of natural surface topographies to generate advanced cell culture substrates
Authors: N.O. Monteiro, J.F. Fangueiro, R.L. Reis, N.M. Neves
Journal: Bioactive Materials (2023)

Surface topographies of cell culture substrates can be used to generate in vitro cell culture environments similar to the in vivo cell niches. In vivo, the physical properties of the extracellular matrix (ECM), such as its topography, provide physical cues that play an important role in modulating cell function. Mimicking these properties remains a challenge to provide in vitro realistic environments for cells. Artificially generated substrates' topographies were used extensively to explore this important surface cue. More recently, the replication of natural surface topographies has been enabling to exploration of characteristics such as hierarchy and size scales relevant for cells as advanced biomimetic substrates. These substrates offer more realistic and mimetic environments regarding the topographies found in vivo. This review will highlight the use of natural surface topographies as a template to generate substrates for in-vitro cell culture. This review starts with an analysis of the main cell functions that can be regulated by the substrate's surface topography through cell-substrate interactions. Then, we will discuss research works wherein substrates for cell biology decorated with natural surface topographies were used and investigated regarding their influence on cellular performance. At the end of this review, we will highlight the advantages and challenges of the use of natural surface topographies as a template for the generation of advanced substrates for cell culture.
Erratum. The Incidence of Diabetes Among 2,777,768 Veterans With and Without Recent SARS-CoV-2 Infection. Diabetes Care 2022;45:782–788
Authors: Pandora L. Wander, Elliott Lowy, Lauren A. Beste, Luis Tulloch-Palomino, Anna Korpak, Alexander C. Peterson, Steven E. Kahn, Edward J. Boyko
Journal: Diabetes Care (2023)

For the article cited above, an issue in the way the outcome (diabetes status) was coded was identified during a follow-up analysis. Participants with ICD-10 codes for diabetes at any time were excluded from the analysis, and incident diabetes was identified based only on laboratory values and glucose-lowering medications. This resulted in a substantial underestimate of the number of cases of incident diabetes in the cohort. The coding issue was corrected, the analysis was repeated, and the corrected code was validated by an independent analyst. After these steps, in agreement with the original article, there remained a statistically significant and positive association of SARS-CoV-2 infection with incident diabetes in the corrected analysis. The largest differences between the original and corrected analysis were seen in the analyses of all male participants in whom the association of SARS-CoV-2 infection with incident diabetes was attenuated in the corrected analysis compared with the original results (odds ratio 120 days: 2.56 [2.32–2.83] original vs. 1.75 [1.63–1.88] corrected; odds ratio all-time: 1.95 [1.80–2.12] original vs. 1.44 [1.36–1.52] corrected). For hospitalized male participants, the differences were smaller. In agreement with the original article, there was no association of SARS-CoV-2 infection with incident diabetes in women in the corrected analysis. Finally, in the corrected models, the P values for the sex * SARS-CoV-2 infection interaction terms were statistically significant except for participants hospitalized in the first 30 days (all available follow-up time). The authors apologize for the error. The online version of the article (https://doi.org/10.2337/dc21-1686) has been updated with the corrected data.
Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop
Authors: Guy Travis Clifton, Mace Rothenberg, Paolo Antonio Ascierto, Glenn Begley, Michael Cecchini, Joseph Paul Eder, Francois Ghiringhelli, Antoine Italiano, Marina Kochetkova, Rong Li, Fatima Mechta-Grigoriou, Sara I Pai, Paolo Provenzano, Ellen Puré, Antoni Ribas, Kurt A Schalper, Wolf Herve Fridman
Journal: Journal for ImmunoTherapy of Cancer (2023)

Checkpoint inhibitors represent an effective treatment approach for a variety of cancers through their inhibition of immune regulatory pathways within the tumor microenvironment (TME). Unfortunately only a minority of patients with cancer achieve clinical benefit from immunotherapy, with the TME emerging as an important predictor of outcomes and sensitivity to therapy. The extent and pattern of T-cell infiltration can vary prominently within/across tumors and represents a biological continuum. Three immune profiles have been identified along this continuum: ‘immune-desert’ or ‘T-cell cold’ phenotype, ‘immune-active’, ‘inflamed’, or ‘T-cell hot’ phenotype, and ‘immune excluded’ phenotype. Of the three profiles, immune excluded remains the most ill-defined with no clear, universally accepted definition even though it is commonly associated with lack of response to immune checkpoint inhibitors and poor clinical outcomes. To address this, 16 multidisciplinary cancer experts from around the world were invited to participate in a symposium using a three-round modified Delphi approach. The first round was an open-ended questionnaire distributed via email and the second was an in-person discussion of the first round results that allowed for statements to be revised as necessary to achieve a maximum consensus (75% agreement) among the rating committee (RC). The final round questionnaire was distributed to the RC via email and had a 100% completion rate. The Delphi process resulted in moving us closer to a consensus definition for immune exclusion that is practical, clinically pertinent, and applicable across a wide range of cancer histologies. A general consensus of the role of immune exclusion in resistance to checkpoint therapy and five research priorities emerged from this process. Together, these tools could help efforts designed to address the underlying mechanisms of immune exclusion that span cancer types and, ultimately, aid in the development of treatments to target these mechanisms to improve patient outcomes.
AB1224 FREQUENCY OF OSTEOPOROTIC THORACIC VERTEBRAL FRACTURES DETECTED AS INCIDENTAL FINDINGS ON INPATIENT CT SCANS
Authors: D. Guevara, L. Ávila Garzón, M. Villamizar Téllez, L. Cardona, C. Ibañez, J. Cajamarca-Baron, A. Escobar, E. Calvo, A. Rojas-Villarraga
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoporosis is one of the main public health problems, leading to the appearance of fragility fractures. Within these, there are vertebral fractures, which in their vast majority have an asymptomatic course, which is why they are presented as incidental findings in imaging studies. <h3>Objectives</h3> To estimate the prevalence of insufficiency fractures in the thoracic vertebrae in patients hospitalized for any cause in a Hospital in Bogotá (Colombia). <h3>Methods</h3> Cross-sectional study in a sub population of Latin American patients, older than 50 years with chest tomography indicated during hospitalization in 2020 for reasons other than suspicion of vertebral bone disease. Patients with secondary causes of vertebral fracture, trauma and spinal instrumentation were excluded. Reading by two independent expert researchers with Genant's semiquantitative visual method and the ABQ method. Clinical and sociodemographic variables were captured (RedCap).Descriptive statistical analysis (STATA 17). The project was approved by the ethics committee. <h3>Results</h3> A total of 317 patients with a mean age of 69.4 years and a predominance of males (57.1%) were included. The most frequent personal history was active smoking (15.8%), use of glucocorticoids in the last 5 years (12.9%), and alcohol consumption (7.5%). A prevalence of vertebral fractures of 8.5% was found, being more frequent in women in 51.8% of the cases, with T11 as the most frequent location (See Table 1 and Figure 1). Only two vertebrae did not define a fracture according to the ABQ method compared to Genant. A disagreement was found in 77.7% of the cases with respect to the final report. <h3>Conclusion</h3> The prevalence of vertebral fractures reported here is lower than that reported in the literature when x-ray imaging is used; it is possible that the use of the tomography influences this result and possibly allows a more objective assessment. Careful evaluation of chest tomographic studies performed during the hospital stay may contribute to an opportune diagnosis of insufficiency fracture associated with osteoporosis. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1231 PROFILE OF OSTEOPOROSIS IN YOUNG WOMEN: EXPERIENCE FROM A POPULATION IN SOUTHERN MOROCCO
Authors: H. Tebaa, H. Arabi, A. Mougui, I. El Bouchti
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoporosis is a generalized skeletal disease characterized by low bone density and alterations in bone microarchitecture. Current definitions and recommendations focus more on postmenopausal osteoporosis with a low number of studies in young pré-menopausal women, which makes it difficult to estimate the prevalence of osteoporosis in this population. <h3>Objectives</h3> To establish the prevalence and determine the etiologies of osteoporosis in young women and their management according to the experience of our department. <h3>Methods</h3> Retrospective descriptive and analytical study including 97 female patients aged less than 45 years, who performed a bone densitometry measurement between the years 2014 and 2022. Data were collected from the bone densitometry database. Osteoporosis was retained if a T score less than or equal to -2.5. Women older than 45 years and or followed for genetic osteopathy were excluded from this study. <h3>Results</h3> There were 97 patients with osteoporosis in this study. The average age was 25 years. Early menopause was found in 15% of cases (10% of cases after chemotherapy). Osteoporosis secondary to endocrinopathy was found in 17% of cases (5% diabetes, 10% primary hyperparathyroidism, 2% Cushing's syndrome). It was secondary to a systemic disease or chronic inflammatory rheumatism in 45% of cases (29% rheumatoid arthritis, 12% spondyloarthropathy, 3% systemic lupus erythematosus and 1 % Horton's disease). The other pathologies found were chronic renal failure in 3% of cases, a notion of prolonged use of corticosteroids in 21% and hormone therapy for breast neoplasia in 14%. 3% of the patients had at least one osteoporotic vertebral fracture. The mean bone mineral density (BMD) in both femurs was 0.727g/cm2. The mean BMD in the spine was 0.965g/cm2. 11% of these patients were treated with oral anti-osteoporotic drugs, 35% were supplemented with vitamin D and calcium. <h3>Conclusion</h3> The discovery of osteoporosis is rare in young women, hence the scarcity of studies in this category of women. It may be of metabolic or drug-induced origin or related to other chronic inflammatory diseases. It should be investigated in the presence of risk factors in order to limit the risk of bone fractures. <h3>Reference</h3> [1]<b>Pepe J, Body J, Hadji P, McCloskey E, Meier C, Obermayer-Pietsch B, et al.</b> Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF. The Journal of Clinical Endocrinology &amp; Metabolism. 2020 Aug 1;105(8):2487-506. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Plasma and intraperitoneal pharmacokinetics of ceftazidime/avibactam in peritoneal dialysis patients
Authors: Valentin al Jalali, Peter Matzneller, Anh Duc Pham, Wisse van Os, Michael Wölfl-Duchek, Maria Sanz-Codina, Andreas Vychytil, Birgit Reiter, Thomas Stimpfl, Markus Zeitlinger
Journal: Clinical Microbiology and Infection (2023)

Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the peritoneal dialysis programme. Ceftazidime/avibactam (CAZ/AVI) is a potential treatment option for APD patients with peritonitis caused by resistant Gram-negative bacteria, but limited data exist on systemic and target-site pharmacokinetics (PK) in patients undergoing APD. This study set out to investigate the PK of CAZ/AVI in plasma and peritoneal dialysate (PDS) of patients undergoing APD.A prospective, open-label PK study was conducted on eight patients undergoing APD. CAZ/AVI was administered as a single intravenous dose of 2 g/0.5 g over 120 minutes. APD cycles were initiated 15 hours after the study drug administration. Dense PDS and plasma sampling was performed for 24 hours after the start of administration. PK parameters were analysed with population PK modelling. Probability of target attainment (PTA) was simulated for different CAZ/AVI doses.PK profiles of both drugs in plasma and PDS were similar, indicating that the two drugs are well suited for a fixed-dose combination. A two-compartment model best described the PK of both drugs. A single dose of 2 g/0.5 g CAZ/AVI led to concentrations that far exceeded the PK/PD targets of both drugs. In the Monte Carlo simulations, even the lowest dose (750/190 mg CAZ/AVI) achieved a PTA of >90% for MICs up to 8 mg/L (The European Committee on Antimicrobial Susceptibility Testing epidemiological cut-off value for Pseudomonas aeruginosa) in plasma and PDS.On the basis of PTA simulations, a dose of 750/190 mg CAZ/AVI would be sufficient to treat plasma and peritoneal fluid infections in patients undergoing APD.
Recent Advances of Emerging Spleen‐Targeting Nanovaccines for Immunotherapy
Authors: Xuanyi He, Jing Wang, Yuqing Tang, Seok Theng Chiang, Tianzhen Han, Qi Chen, Chunxi Qian, Xiaoshuai Shen, Rongxiu Li, Xiangzhao Ai
Journal: Advanced Healthcare Materials (2023)

Abstract Vaccines provide a powerful tool to modulate the immune system for human disease prevention and treatment. Classical vaccines mainly initiate immune responses in the lymph nodes (LNs) after subcutaneous injection. However, some vaccines suffer from inefficient delivery of antigens to LNs, undesired inflammation, and slow immune induction when encountering the rapid proliferation of tumors. Alternatively, the spleen, as the largest secondary lymphoid organ with a high density of antigen‐presenting cells (APCs) and lymphocytes, acts as an emerging target organ for vaccinations in the body. Upon intravenous administration, the rationally designed spleen‐targeting nanovaccines can be internalized by the APCs in the spleen to induce selective antigen presentation to T and B cells in their specific sub‐regions, thereby rapidly boosting durable cellular and humoral immunity. Herein, the recent advances of spleen‐targeting nanovaccines for immunotherapy based on the anatomical architectures and functional zones of the spleen, as well as their limitations and perspectives for clinical applications are systematically summarized. The aim is to emphasize the design of innovative nanovaccines for enhanced immunotherapy of intractable diseases in the future.
Current Trends in Anti-Aging Strategies
Authors: Robert S. Rosen, Martin L. Yarmush
Journal: Annual Review of Biomedical Engineering (2023)

The process of aging manifests from a highly interconnected network of biological cascades resulting in the degradation and breakdown of every living organism over time. This natural development increases risk for numerous diseases and can be debilitating. Academic and industrial investigators have long sought to impede, or potentially reverse, aging in the hopes of alleviating clinical burden, restoring functionality, and promoting longevity. Despite widespread investigation, identifying impactful therapeutics has been hindered by narrow experimental validation and the lack of rigorous study design. In this review, we explore the current understanding of the biological mechanisms of aging and how this understanding both informs and limits interpreting data from experimental models based on these mechanisms. We also discuss select therapeutic strategies that have yielded promising data in these model systems with potential clinical translation. Lastly, we propose a unifying approach needed to rigorously vet current and future therapeutics and guide evaluation toward efficacious therapies.
BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond
Authors: Andrew H. Wei, Andrew W. Roberts
Journal: HemaSphere (2023)

Altering the natural history of acute myeloid leukemia (AML) in unfit and older patients has proved a highly challenging hurdle, despite several decades of concerted clinical trial effort. The arrival of venetoclax (VEN) to the clinical stage represents the most important therapeutic advance to date for older patients with AML. In this review, we will explain how and why VEN works, summarize its remarkable pathway to regulatory approval, and highlight the key milestones that have been important for its successful development in AML. We also provide perspectives on some of the challenges associated with using VEN in the clinic, emerging knowledge regarding mechanisms of treatment failure, and current clinical research directions likely to shape how this drug and others in this new class of anticancer agents are used in the future.